Cell-mediated xenoresponses: strong or weak?

Cell-mediated responses to xenoantigens are different from those to alloantigens. CD4+ T cells are especially important in xenoresponses and depletion of CD4+ T cells can prolong survival of xenografts better than allografts in some circumstances. The difference between the two responses is due in part to the relative weakness of direct T-cell responses stimulated by xenogeneic antigen-presenting cells. Instead, T cells tend to require that donor antigens be processed and presented indirectly in association with the MHC antigens on their own APCs. The defect in direct stimulation is due to failure of some of the several T cell/APC interactions when the receptors and ligands of these interactions come from different species. Although the cell-mediated response to xenografts is different, it remains very strong. The mechanism by which CD4+ cells cause xenograft destruction remains to be determined, but a better understanding of this mechanism may help to select the most useful types of immunosuppression for xenogeneic transplantation.